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Abstract

Background

Spirooxindoles have been reported to be effective anticancer drug candidates by displaying promising pre-clinical results. Therefore, to find out a lead spirocyclic oxindole template, a series of spirooxindole derivatives bearing pyrrolizidine () and -methyl pyrrolidine () were synthesized using an efficient multicomponent, one-pot, and stereoselective [3+2] cycloaddition reaction and evaluated against HT29 and HCT116 human colon cancer cell lines.

Methods

The pyrrolizidine and N-methyl pyrrolidine spirooxindole derivatives were synthesised in excellent regio- and stereoselectivity using previously optimized reaction conditions. They were evaluated against cell lines HT29 and HCT116. ADME profiling, molecular docking, and dynamics simulation studies were performed to ascertain the probable mode of action of the lead derivative.

Results and Discussion

The spirooxindoles were characterized using FTIR, ESI-MS, 1H and 13C NMR, purity was determined by RP-HPLC, and stereochemistry was confirmed by X-ray crystallography. Compound produced the best anti-colon cancer activity with IC values of 62.66 and 9.55 µM against HT29 and HCT116 human colon cancer cell lines, respectively. The studies revealed that MDM2 protein inhibition is a probable mode of anti-colon cancer activity, supported by the data obtained in the molecular docking and molecular dynamics study.

Conclusion

The described [3+2] cycloaddition reaction proved to be a highly efficient and catalyst-free reaction. The cell viability assays and studies revealed that more spirooxindoles can be designed with a varied degree of substitution to target colon cancer.

© 2026 The Author(s). Published by Bentham Science Publishers.
This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode
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2026-01-16
2026-02-24

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Stereoselective Synthesis, Anticolon Cancer Activity, Molecular Docking, and Dynamics Simulation Studies of Spirooxindole Derivatives
Bentham Science Publishers ; https://doi.org/10.2174/0109298673408088251031103739
/content/journals/cmc/10.2174/0109298673408088251031103739
/content/journals/cmc/10.2174/0109298673408088251031103739
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The Supporting Information includes 1H, 13C-NMR spectra, mass spectra, HPLC chromatograms, dose-response curves, and data (Figs. to ).

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  • Article Type:     Research Article
Keywords: multicomponent reaction ; One-pot reaction ; spirooxindoles ; azomethine ylide ; molecular docking ; colon cancer cell lines ; dynamics ; stereoselective synthesis

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